Interleukin-1 beta modulation of norepinephrine release from rat myenteric nerves

We examined the ability of human recombinant interleukin-1 beta (hrIL-1 beta) to alter the release of [3H]norepinephrine ([3H]NE) by KCl or electrical field stimulation in longitudinal muscle-myenteric plexus of rat intestine. The cytokine had no immediate effect on either the basal or evoked release of [3H]NE. However, hrIL-1 beta caused a biphasic time-dependent suppression of evoked [3H]NE release that was delayed in onset. IL-1 beta also stimulated the cycloheximide-sensitive uptake of [35S] methionine uptake by the tissue. The initial suppression of [3H]NE release was observed after 30 min and could not be inhibited by cycloheximide. A delayed peak was observed after 120 min and was inhibited by cycloheximide. The effect of IL-1 beta was maximal at 10 ng/ml and could be prevented by a neutralizing anti-IL-1 beta antibody or by preincubating the tissue with an IL-1-receptor antagonist. These results indicate that IL-1 beta suppresses [3H]NE release from rat myenteric plexus by two mechanisms, one of which is independent of protein synthesis and the other of which is mediated by endogenous IL-1.